More than two-thirds of patients with advanced cancer suffer from pain. Persistent pain in cancer is a combination of nociceptive pain from tissue infiltration and inflammation, and neuropathic pain from patients seek complementary and alternative therapies such as nutritional supplements and herbal medicines to alleviate their unmitigated pain. Scientific data on the efficacy and mechanisms of action of these therapies for pain are lacking. Preliminary studies in our laboratories indicate that a soy diet prevents the development of neuropathic pain in an animal model of partial nerve injury and that tart cherries have antioxidant and anti- inflammatory effects. This proposal will examine the analgesic effects of soy and tart cherry as dietary supplements in four different well- established animal models of chronic pain which represent different aspects of pain associated with cancer: a model of chronic inflammation, two models of partial nerve injury, a model of cytotoxic neuropathy, and a model of bone cancer pain (Sp.Aim 1). The mechanisms underlying the analgesic effects of the soy and tart cherry dietary supplements will be investigated with regard to their interaction with opiate receptors and their effects on the inflammatory process (Sp. Aim 2). These animal models of chronic pain will also be used to investigate the role and mechanism of analgesia of selected, promising traditional Indian, Chinese, and Japanese herbal medicines (Sp. Aim 3). Behavioral studies in rats and mice will be complemented by biochemical assays of cytokines in tissue and serum, and serum levels of isoflavonoids and anthocyanins. The results of these studies should provide new insights into the potential role of complementary therapies for cancer pain and will further our understanding of the mechanisms of interaction of natural dietary and herbal ingredients with the pain signaling process. Data from these studies will be used to select promising candidate herbs for future clinical trials.